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Biomedical subjects

S M Haffner

Publications and source records attributed to S M Haffner.

At least 127 records · Page 7Linked to original sources

Glibenclamide, but not acarbose, increases leptin concentrations parallel to changes in insulin in subjects with NIDDM.

OBJECTIVE: To hypothesize if glibenclamide, which increases insulin levels, also increases leptin concentrations. RESEARCH DESIGN AND METHODS: Leptin is a hormone that regulates weight in mice. In obese humans, leptin concentrations are increased, suggesting resistance to the effects of this hormone. Although short-term infusion of insulin during the hyperinsulinemiceuglycemic clamp does not increase leptin concentration, the effect of oral antidiabetic agents on leptin concentration is unknown. Differing effects can be expected, since glibenclamide acts via stimulation of insulin secretion, whereas acarbose inhibits alpha-glucosidases of the small intestine and has no direct effect on insulin levels. We examined the effect of acarbose (n = 4), glibenclamide (n = 6), and placebo (n = 6) on insulin and leptin levels during 24-h periods before and after 16 weeks of therapy. RESULTS: We observed a significant diurnal variation in leptin concentrations. This was inversely related to insulin levels during the 24-h follow-up with usual diet. Neither the placebo nor acarbose altered leptin concentrations. However, glibenclamide increased leptin concentrations parallel to insulin levels. There were only minor changes in body weight during the l6-week follow-up: decrease in the placebo group (change -0.5 kg/m2, P = 0.07) and acarbose (change -0.7 kg/m2, P = 0.046) and increase in the glibenclamide group (change 0.8 kg/m2, P = 0.27). However, individual subjects who gained weight had increases in their leptin concentrations. The diurnal variation in leptin concentrations was preserved after glibenclamide. CONCLUSIONS: Glibenclamide increases circadian leptin and insulin concentrations, whereas acarbose does not. This observation may help to explain weight gain in subjects treated with glibenclamide and stable weight in those treated with acarbose in the long run.

Acarbose↗

High prevalence of cholelithiasis in a low income Mexican population: an ultrasonographic survey.

The authors present the results of a population-based survey of cholelithiasis carried out in a low-income area of Mexico City using high-resolution gallbladder ultrasound. The purpose of the study was to estimate the prevalence and selected associated risk factors of cholelithiasis (CL). The population of the studied area was 15,532 subjects, of whom 3,505 (22.6%) were eligible for the baseline survey (men and non-pregnant women between 35-64 years of age). Of this group, 1,735 (76.03%, 702 men and 1,033 women) were located for a follow-up study. Ultrasonography was performed on all except for 100 subjects who had undergone previous cholecystectomy. Crude prevalence of CL was 14.1% (95% CI 12.5-15.5). The prevalence was 5.8% (95% CI 4.1-7.5) in men and 19.7% (95% CI 17.3-22.1) in women. Presence of gallstones was associated with age, sex (men p<0.006, women p<0.001), and multiparity (p<0.002). Centrality index in men and body mass index in women were positive and significantly associated with CL when compared with subjects without CL. High levels of fasting and post-glucose load insulin in women and men respectively were associated with CL. The authors conclude that the population of this study has a high prevalence of CL and confirm some known risk factors such as age, sex, BMI and multiparity. Proper assessment of the magnitude problem and characterization of potentially modifiable risk factors will play a major role in preventing this pathology.

Adult↗

Effects of cigarette smoking, diabetes, high cholesterol, and hypertension on all-cause mortality and cardiovascular disease mortality in Mexican Americans. The San Antonio Heart Study.

Despite high levels of cardiovascular risk factors, Mexican Americans paradoxically have a lower prevalence of cardiovascular disease. A possible explanation is that conventional cardiovascular risk factors have a lesser impact on this ethnic group. In the present study, a 7- to 8-year follow-up of the San Antonio Heart Study cohort was used to estimate total and cardiovascular disease mortality and their association with baseline risk factors. A total of 2,629 Mexican Americans form the basis of this study, and 1,136 non-Hispanic whites from the same cohort served as the comparison group. The age- and sex-adjusted rates for total death and cardiovascular disease death were somewhat higher in Mexican Americans than non-Hispanic whites (rate ratio for total mortality = 1.4, 95% confidence interval 1.0-2.0; and rate ratio for cardiovascular mortality = 1.3, 95% confidence interval 0.7-2.4). After adjustment for sex, age, and socioeconomic status in multivariate analyses, current smoking, diabetes, high cholesterol, and hypertension were positively associated with all-cause mortality and cardiovascular disease mortality in Mexican Americans. Overall, these risk factors accounted for 45% of all-cause mortality and 55% of cardiovascular disease mortality in this ethnic group. In comparison, the risk factors accounted for 46% of all-cause mortality and 46% of cardiovascular disease mortality in non-Hispanic whites. The authors conclude that cigarette smoking, diabetes, high cholesterol, and hypertension are important predictors of both all-cause and cardiovascular disease deaths in Mexican Americans. There was no evidence for a diminished effect of these risk factors in Mexican Americans.

Adult↗

Metabolic precursors of hypertension. The San Antonio Heart Study.

BACKGROUND: The relation of possible metabolic precursors (especially insulin resistance) to hypertension has been controversial. In addition, these associations may differ by level of obesity or ethnicity. METHODS: We followed up 1039 initially nondiabetic, nonhypertensive subjects from the San Antonio Heart Study for 7 years. RESULTS: Hypertension developed in 93 subjects. Age, body mass index, waist-to-hip ratio, and fasting insulin and triglyceride levels predicted the development of hypertension in univariate analyses. After adjustment for age, body mass index, waist-to-hip ratio, gender, ethnicity, and fasting glucose levels, higher levels of triglyceride and fasting insulin predicted the development of hypertension. Body mass index and fasting insulin and triglyceride levels predicted the development of hypertension in Mexican Americans and non-Hispanic whites. In addition, fasting insulin levels predicted the development of hypertension in lean and obese subjects. Increased insulin secretion (as judged by the 30-minute insulin increment) on an oral glucose tolerance test also predicted the development of hypertension. CONCLUSIONS: A cluster of atherogenic changes may precede the development of hypertension, and increased fasting insulin concentration predicts hypertension in important subgroups of subjects.

Adult↗

Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

Few prospective data are available regarding the association of sex hormone-binding globulin (SHBG), testosterone, and the risk of developing diabetes. Stored fasting serum samples from participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) at 22 centers throughout the United States from December 1973 through February 1976 were used to perform a nested case- control study. For 176 initially nondiabetic men who had developed diabetes during 5 years of follow-up, two controls were selected, one matched only for randomization date, treatment group, and clinic ("loose controls") and the other matched additionally for fasting glucose and body mass index ("tight controls"). When cases were compared with lose controls, higher levels of fasting insulin and lower levels of total and free testosterone and SHBG were significantly associated with increased development of diabetes. However, when cases were compared with tightly matched controls, these associations weakened considerably. Low SHBG and testosterone may constitute part of the prediabetic state in men along with previously reported variables, such as higher glucose and insulin levels and obesity.

Adult↗

Genetic correlations between lipoprotein phenotypes and indicators of sex hormone levels in Mexican Americans.

Previous studies have shown that the inverse relationship between HDL cholesterol (HDL-C) and triglyceride (TG) levels, risk factors for cardiovascular disease, is due largely to the effects of shared genes. HDL-C and TG are also known to be related to endogenous sex hormone levels, however the nature of the relationships is unclear. The objective of this study is to ascertain the extent to which these relationships are determined by shared genes. We conducted a multivariate quantitative genetic analysis of HDL-C, TG, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) in 635 people from 27 pedigrees participating in the San Antonio Family Heart Study. Heritabilities (h2) and genetic and environmental correlations (rho G and rho E) were estimated simultaneously by maximum likelihood methods. All four traits showed significant (P < 0.05) heritabilities: h2HDL-C = 0.38, h2TG = 0.54, h2DHEAS = 0.43, h2SHBG = 0.26. Significant genetic correlations were detected between HDL and each of the other traits: rho G(HDL-TG) = -0.56, rho G(HDL-DHEAS) = 0.23 and rho G(HDL-SHBG) = -0.56. However, there were no significant genetic correlations between TG and either measure of sex hormones. Thus, at least three separate groups of genes influence HDL-C levels in Mexican Americans: one group that has pleiotropic effects on HDL and TG, one group influences both HDL-C and SHBG and a third influences both HDL-C and DHEAS.

Adipose Tissue↗

Decreased insulin action and insulin secretion predict the development of impaired glucose tolerance.

The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of impaired glucose tolerance (IGT) is controversial. Few prospective data are available on metabolic precursors of IGT. We examined the relation of fasting serum insulin level (as a marker of insulin resistance) and change in insulin/glucose ratio (delta I30/ delta G30) over the first 30 min after glucose ingestion (as a marker of insulin secretion) as predictors of the 7-year development of IGT in 839 Mexican Americans and non-Hispanic whites with normal glucose tolerance at baseline from the San Antonio Heart Study. IGT eventually developed in 148 subjects. When modelled separately, fasting serum insulin (odds ratio (OR) = 2.60, 95% confidence interval (CI) = 1.58, 4.28, p < 0.005), but not delta I30/ delta G30 (OR = 0.80, 95% CI = 0.50, 1.27, p = 0.339) predicted the development of IGT. However, when both variables were included in the same logistic regression model, fasting serum insulin (OR = 3.50, 95% CI = 1.97, 6.21, p < 0.001) and low delta I30/ delta G30 (OR = 0.48, 95% CI = 0.28, 0.82, p = 0.008) both predicted IGT. These results were basically unchanged after further adjustment for obesity, body fat distribution and fasting plasma glucose level. We conclude that both decreased insulin secretion (as assessed by low delta I30/ delta G30) and increased insulin resistance (as assessed by fasting serum insulin) predict the development of IGT and are thus early precursors of non-insulin-dependent diabetes mellitus; further studies of insulin secretion should take into account the level of basal insulin resistance.

Adult↗

Apolipoprotein B (apo B) signal peptide length polymorphisms are associated with apo B, low density lipoprotein cholesterol, and glucose levels in Mexican Americans.

We investigated the effects of apolipoprotein (apo) B signal peptide length polymorphisms on low density lipoprotein cholesterol (LDL-C), apo B, and post-challenge (2 h) glucose levels in 686 Mexican Americans from 34 families. The most common allele encoded an apo B signal peptide of 27 amino acids (ins; SP-27), the next most frequent allele encoded a 24 amino acid signal peptide (del; SP-24), and the rarest allele encoded a 29 amino acid signal peptide (ins; SP-29) that has been found only in Mexican Americans. Homozygotes for the SP-24 allele had significantly higher mean levels of apo B. LDL-C, and 2-h glucose than SP-27 homozygotes, and SP-27/SP-24 heterozygotes had intermediate levels (P = 0.01 for apo B, P < 0.001 for LDL-C, and P = 0.04 for 2-h glucose). Heterozygotes for the SP-29 allele had higher apo B and LDL-C levels compared to homozygotes for the SP-27 or SP-24 alleles. Apo B signal peptide length polymorphism accounted for 4.2%, 3.5%, and 3.0% of the residual variation in LDL-C, apo B, and 2-h glucose levels, respectively, among the Mexican American families.

Adolescent↗

Plasma oxidizability in Mexican-Americans and non-Hispanic whites.

Several lines of evidence support an atherogenic role for oxidized low-density lipoprotein (LDL). Previous studies have suggested that although Mexican-Americans have an increased rate of diabetes, obesity, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels, their rates of coronary heart disease (CHD) are similar or possibly lower than in non-Hispanic whites. Mexican-Americans have smaller, denser LDL than non-Hispanic whites. On the basis of this latter observation, we postulated that lipid peroxide (LPO) levels would be increased in Mexican-Americans. We examined the oxidizability of plasma in 50 Mexican-Americans and 50 non-Hispanic whites from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease, at baseline and after coincubation with a metal-independent system (2'2'-azobis-2-amidinopropane hydrochloride [AAPH]) and a metal-dependent system (Fe2+/H2O2) of oxidation. LPO levels were measured by a modified fluorimetric assay. Vitamin E and plasma fatty acid composition were also determined. We found significantly higher LPO levels at baseline and after AAPH coincubation in Mexican-Americans than in non-Hispanic whites (baseline, 2.75 +/- .09 v 2.07 +/- .09 micromol/L, P < .001; post-AAPH, 5.49 +/- .14 v 5.07 +/-. .04 micromol/L, P = .037). However, no significant ethnic differences were seen after coincubation with Fe2+/H2O2. Diabetes and cigarette-smoking were also associated with higher LPO levels. Mexican-Americans also had lower levels of vitamin E (the predominant lipid-soluble antioxidant in plasma) than non-Hispanic whites, although these differences only partially explained the differences in susceptibility to oxidation. Plasma fatty acids were similar in Mexican-Americans and non-Hispanic whites, suggesting only small differences in diet composition. We conclude that LPO levels are higher in Mexican-Americans than in non-Hispanic whites, and that these results are only partially related to differences in vitamin E levels.

Adult↗

Migration status, socioeconomic status, and mortality rates in Mexican Americans and non-Hispanic whites: the San Antonio Heart Study.

It has been claimed that Mexican Americans have a favorable mortality experience despite their low socioeconomic status (SES). The present study compared all-cause mortality of non-Hispanic whites with that of United States-born and foreign-born (i.e., born in Mexico) Mexican Americans. Subjects were 3735 residents of San Antonio, TX, who were followed-up for 7-8 years. The sex-age adjusted death rates per 1000 person-years were higher for United States-born Mexican Americans (5.7) than for non-Hispanic whites (3.8) or for foreign-born Mexican Americans (3.6). Foreign-born Mexican Americans had the lowest socioeconomic status (SES), and non-Hispanic whites had the highest SES. After adjustment for SES, the mortality ratio for United States-born Mexican Americans compared with foreign-born Mexican Americans was 1.9 (95% confidence interval, 1.0-3.5), while the ratio for United States-born Mexican Americans compared with non-Hispanic whites was 1.0 (95% confidence interval, 0.7-1.6). Stratified analysis revealed that those in the lowest SES tertiles had threefold greater risk of death than those in the highest tertiles among both United States-born Mexican Americans and non-Hispanic whites (test for trend, P < 0.001). These data suggest that lower SES is strongly associated with increased mortality. After adjustment for SES, mortality rates were similar for United States-born Mexican Americans and non-Hispanic whites. Foreign-born Mexican Americans had the lowest mortality rates of the three groups.

Adult↗

Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland.

OBJECTIVE: It has been suggested that Chlamydia pneumoniae, a Gram-negative intracellular bacterium, is a risk factor for both myocardial infarction and chronic coronary heart disease. Previous studies have been done predominantly in non-diabetic subjects and thus the effect of diabetes on the association between C. pneumoniae antibodies and coronary heart disease has not been analysed. The aim of our study was to investigate the association between prior chlamydial infection and the risk of serious coronary heart disease events (myocardial infarction or coronary death) in a 7-year prospective study of cohorts of diabetic and non-diabetic subjects in two areas of Finland. RESULTS: It was found that the prevalence of elevated chlamydial antibodies at baseline was higher in nondiabetic subjects who had serious coronary heart disease events during the follow-up than in subjects without coronary heart disease events (32 vs 15%, relative risk 2.56, P = 0.013) in East Finland. In non-diabetic subjects living in West Finland we did not find this association. The association between the C. pneumoniae antibodies and coronary heart disease events did not markedly change after controlling for other risk factors for coronary heart disease (OR 2.44, P = 0.055) in non-diabetic subjects living in eastern Finland. In diabetic patients we did not find any association between chlamydial antibodies and coronary heart disease events. CONCLUSION: We found an association between C. pneumoniae antibodies and coronary heart disease events in non-diabetics living in eastern Finland. This association remained strong even after controlling for the other risk factors for coronary heart disease. In diabetic patients with high risk for coronary heart disease, C. pneumoniae was not a risk factor for coronary heart disease.

Acute Disease↗

Relationship of plasma insulin concentration and insulin sensitivity to blood pressure. Is it modified by obesity?

OBJECTIVE: To investigate the relationship between insulin level, insulin sensitivity and blood pressure in normoglycaemic men (n = 51) and women (n = 64) aged 53-61 years who were not receiving blood pressure medication and were participants in a previous population-based study. METHODS: Insulin sensitivity was estimated by the minimal model from a frequently sampled intravenous glucose tolerance test. RESULTS: Systolic blood pressure (SBP) did not correlated significantly with fasting insulin level, 2 h insulin level or insulin sensitivity. Diastolic blood pressure (DBP) correlated positively with fasting insulin level but not with 2 h insulin level or insulin sensitivity. However, the positive association between fasting insulin level and DBP was not significant after adjustment for obesity and age. The relationship between high fasting insulin concentration and high DBP was stronger in lean than in obese subjects. The positive correlation between fasting insulin level and DBP was significant in lean but not in obese subjects. CONCLUSIONS: The relationships between decreased insulin sensitivity and compensatory hyperinsulinaemia and blood pressure were rather weak. It is possible that different mechanisms may control blood pressure in lean and obese subjects, with a weaker association between insulin level and blood pressure in obese subjects. Alternatively, in obese subjects long-standing hyperinsulinaemia might increase blood pressure by mechanisms such as sympathetic activation and effects of vasculature, which may mask the underlying contribution of hyperinsulinaemia.

Aged↗

Sex hormone-binding protein, hyperinsulinemia, insulin resistance and noninsulin-dependent diabetes.

Possible data complicating sex hormones, especially testosterone, in the etiology of cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM) comes from the much higher rates of cardiovascular disease in men than in women. Pharmacological administration of anabolic steroids to both men and women increases glucose and insulin concentrations and also insulin resistance. In vivo assessment of sex hormones and binding proteins in both premenopausal and postmenopausal women has suggested that increased free testosterone and decreased sex hormone-binding globulin (SHBG) is associated with higher glucose and insulin concentrations. In a few studies, increased insulin resistance has been associated with decreased SHBG levels. Some data suggests that visceral fat mediated the associates of sex hormones with insulin in women. Little prospective data is available on the association of sex hormones to the development of NIDDM in women but in two studies, low SHBG concentrations predicted NIDDM in Gothenburg and San Antonio. Recently, attention has focused on the role of sex hormones in relation to insulin in men. Surprisingly, higher levels of testosterone have been associated with improved cardiovascular risk factors (such as high-density lipoprotein cholesterol) and lower glucose and insulin levels. Total testosterone and SHBG have been associated with defects in nonoxidative glucose disposal and upper body adiposity in normoglycemic Finnish men. The latter observation is of interest since specific defects in nonoxidative glucose disposal are observed in normoglycemic relatives of subjects with NIDDM. The temporal relationship between sex hormones and insulin has been controversial. The traditional view of sex hormones increasing insulin resistance has been challenged in women by studies showing that insulin stimulates androgen production in the ovary. Recent data [JCEM 1995;80:654-658] suggests that insulin stimulates testosterone production and suppresses SHBG production in normal and obese men. On the other hand, administration of testosterone to centrally obese hypogonadal middle-aged men has improved insulin sensitivity.

Anabolic Agents↗

Ultrasonographically assessed maximum carotid artery wall thickness in Mexico City residents and Mexican Americans living in San Antonio, Texas. Association with diabetes and cardiovascular risk factors.

Measurements of carotid artery wall thickness are often used as a surrogate for atherosclerosis. However, few studies have performed these measurements in populations of Mexican origin. Since Mexicans in Mexico City consume high-carbohydrate diets and have carbohydrate-induced dyslipidemia (high triglyceride and low HDL cholesterol levels) compared with Mexican Americans living in San Antonio, Tex, we questioned whether they also had more atherosclerosis than San Antonio Mexican Americans. Mean maximum intimal-medial thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries were measured in 867 subjects aged 35 to 64 years (40% men) in two Mexican-origin populations, one from San Antonio (n = 202) and the other from Mexico City (n = 665). IMT's in the two cities were compared, and their associations with cardiovascular risk factors were analyzed. Older age, male sex, high levels of total cholesterol, low levels of HDL cholesterol, and high systolic blood pressure were positively associated with both CCA IMT and ICA IMT. Cigarette smoking was significantly associated with ICA IMT. CCA and ICA IMTs in diabetic subjects were thicker than in nondiabetic subjects in both men and women (all P < = .05). CCA IMT was thicker in the San Antonio than the Mexico City subjects after adjustment for cardiovascular risk factors (0.81 versus 0.76 mm in men and 0.77 versus 0.71 mm in women; P < .001 for city difference). San Antonio men also had thicker ICA IMT than their counterparts in Mexico City (0.88 versus 0.83 mm), but the reverse was true for women (0.73 versus 0.77 mm; interaction between sex and city, P < .05). Our results indicate that men had higher carotid IMTs than women. CCA IMT was thicker in San Antonio Mexican Americans than in Mexico City residents. The differences in ICA IMTs between San Antonio and Mexico City were inconsistent. Thus, since Mexico City residents consume high-carbohydrate diets, the data do not support an atherogenic effect of such diets. The interaction between sex and city on ICA IMT deserves further study.

Cardiovascular Diseases↗

Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures.

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.

Adult↗

Apolipoprotein E polymorphism and LDL size in a biethnic population.

Polymorphisms in the apolipoprotein E (apoE) phenotype (especially E4) are associated with increased cardiovascular risk and particularly with increased concentrations of LDL cholesterol. Little is known, however, about whether alterations in LDL size are associated with the apoE4 phenotype. LDL size was determined by gradient gel electrophoresis, and apoE phenotype was determined by isoelectric focus in 337 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular risk factors in Mexican Americans and non-Hispanic whites. ApoE4 was associated not only with increases in LDL cholesterol concentrations but also with decreased LDL size. After adjustment for age, sex, body mass index, waist-to-hip ratio, triglyceride, HDL cholesterol, fasting insulin, and diabetic status, the apoE phenotype remained significantly related to LDL size (A) in both men (apoE23, 260.0; apoE33; 256.3; and apoE34, 252.6; P = .01) and women (apoE23, 261.7; apoE33, 257.9; and apoE34, 256.7, P = .045). Variations in apoE phenotype are associated not only with changes in the absolute concentration of LDL cholesterol but also with changes in its composition. These changes are only partly explained by associations of apoE with insulin, triglyceride, and HDL cholesterol.

Adult↗

Ethnic differences in carotid wall thickness. The Insulin Resistance Atherosclerosis Study.

BACKGROUND AND PURPOSE: Ethnic differences in cardiovascular disease (CVD) morbidity and mortality have been observed in US adults. However, little data exist on differences in indices of preclinical atherosclerosis such as carotid wall intima-media thickness (IMT) for US non-Hispanic whites, Hispanics, and blacks. This study was undertaken to determine whether there were ethnic differences in carotid wall IMT. METHODS: Internal carotid artery (ICA) IMT and common carotid artery (CCA) IMT, indices of atherosclerosis, were assessed with the use of B-mode ultrasound in 1020 nondiabetic participants in the Insulin Resistance Atherosclerosis Study, a multicenter study designed to examine the association between insulin resistance and carotid atherosclerosis. The study included 281 blacks, 329 Hispanics, and 410 non-Hispanic whites aged 40 to 69 years. RESULTS: Blacks had significantly greater CCA IMT than non-Hispanic whites (865 versus 808 microns); this remained significant after adjustment for major CVD risk factors and insulin sensitivity (864 versus 823 microns). There were no significant differences in ICA IMT between blacks and non-Hispanic whites. Hispanics had significantly lesser CCA IMT than non-Hispanic whites (749 versus 776 microns), and these differences remained significant after adjustment for traditional cardiovascular risk factors and insulin sensitivity (750 versus 778 microns). There were no significant differences in ICA IMT between non-Hispanic whites and Hispanics. CONCLUSIONS: We conclude that ethnic differences exist in CCA but not in ICA IMT in nondiabetic subjects. These differences in IMT, which are indicators of atherosclerosis, are a non-invasive measure that is consistent with some of the data on clinical end points. These differences may be associated with the observed differences in CVD morbidity and mortality among major ethnic groups in the United States.

Arteriosclerosis↗

Carotid artery intima-media thickness in elderly patients with NIDDM and in nondiabetic subjects.

BACKGROUND AND PURPOSE: The risk of atherosclerotic vascular disease is increased both in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in those with impaired glucose tolerance compared with nondiabetic subjects. Although classic cardiovascular risk factors are operative in subjects with NIDDM, other factors closely related to insulin resistance syndrome such as diabetic dyslipidemia and hyperglycemia itself may contribute to an excessive cardiovascular disease risk in subjects with NIDDM. The purpose of this study was to investigate the carotid intimal-medial thicknesses (IMTs) and their determinants in elderly patients with NIDDM and in control subjects. METHODS: We investigated the common carotid and carotid bifurcation IMTs and their determinants in groups of elderly patients (n = 84, age 67.2 +/- 0.6 years) with NIDDM and in 119 control subjects (21 with impaired and 98 with normal glucose tolerance; ages 67.5 +/- 1.0 and 65.1 +/- 0.6 years, respectively). RESULTS: Common carotid and carotid bifurcation IMTs were greater in the NIDDM group than in control subjects (P < .05 to .01). In NIDDM patients, the mean carotid IMT correlated with postglucose 1-hour plasma insulin (r = .305, P = .01, adjusted for age and sex), serum LDL triglyceride (r = .237, P < .05), and apolipoprotein B concentrations (r = .263, P < .05). Fasting plasma immunoreactive insulin, proinsulin, or specific insulin levels were not significantly associated with carotid IMT. Both diabetic status (P < .05) and the presence of clinical macrovascular disease (P < .01) contributed independently to carotid IMT. CONCLUSIONS: Carotid IMT was greater in NIDDM patients than in control subjects. The main determinants of IMT in NIDDM patients were related to both postglucose insulin levels and abnormal lipoprotein profiles characteristic of NIDDM and insulin resistance syndrome. Treatment of these factors is likely to reduce the atherosclerotic burden in NIDDM.

Aged↗